Cancer is considered to be a disease in which individual molecules are either overproduced, mutated, expressed at inappropriate stages of development, or lost due to inheritance or aberrant mitotic division. The important molecules in this cellular control are growth factors, growth factor receptors, signal transducers, effector enzymes and dominant or recessive oncogenes. The tumors most frequently removed by surgeons have been reported to have changes in one or another of these types of molecules. Phospholipase C-gamma(PLC-gamma) is an important effector enzyme which becomes activated in response to a variety of growth factors and contains two SH2 domains. My main research goals during the fellowship are 1) to study the role of SH2 domains in the activation of PLC-gamma by growth factor receptor tyrosine kinases and other nonreceptor tyrosine kinases and 2) to study the specificity of SH2 domains in the interaction of PLC-gamma with a variety of tyrosine phosphate-containing proteins. During the proposed research, I hope to keep myself up to date with "state of the art" techniques for the expression of proteins in E. Coli, protein purification, peptide synthesis and purification, immunoaffinity chromatography, fluorescence labelling of peptides, site directed mutagenesis, and DNA sequencing. In addition, I want to gain an overview of cell signal transduction involving phosphoinositide turnover. In addition to the activation of PLC by protein tyrosine kinases, the research topics of Dr. Rhee's group include the G-protein dependent modulation of PLC and the metabolism of inositol phosphates.